1. Field of the Invention
The present invention relates to compounds having pharmacological activity, more specifically to non-steroidal anti-inflammatory agents, analgesics and antipyretics, and particularly to a series of 3-[.omega.-(3,5-di-t-butyl-4-hydroxyphenyl)alkanoyl]pyrroles and their de-oxy analogs.
2. Background Information and Related Art
The use of certain pyrroloyl compounds as non-steroidal anti-inflammatory agents is known. For example, U.S. Pat. No. 4,418,074 (to Moore) describes: ##STR1## and reference is made to several other U.S. patents in which substitutions at the 4-position of 2,6-di(t-butyl)phenols are taught, including: an N-substituted carboxamido group (U.S. Pat. No. 4,128,664), an optionally substituted benzoyl group (U.S. Pat. No. 4,124,725), an optionally substituted phenyl group (U.S. Pat. No. 4,172,151), and optionally substituted thiophenyl groups (U.S. Pat. No. 4,172,082).
Other compounds having the di-t-butyl-hydroxyphenyl moiety have been proposed as anti-inflammatory agents, including: ##STR2## [Moore and Swingle, Agents and Actions, 12(5): 674-683 (1982)]; ##STR3## [Moore, Bell and Swingle, "SAR of Antioxidant-Antiinflammatory Agents: Di-t-Butyl Phenols and Other Series", 19th National Medicinal Chemical Symposium of the ACS, Tuscon, AZ, 151-154, June 17-21, 1984]; ##STR4## [Hidaka, et al., Ensho, 3(4): 511-512 (1983)]; 2,6-di-t-butyl-phenols with a heterocyclic group at the 4-position, such as: ##STR5## [Isomura, et al., Chem. Pharm. Bull., 31(9): 3168-3178 (1983)]; ##STR6## and the corresponding 1,1-dioxide [Isomura, et al., Chem. Pharm. Bull., 31(9): 3179-3185 (1983)]; and ##STR7## [Isomura, et al., Chem. Pharm. Bull., 32(1): 152-165 (1984)]. The compound of Formula VIII was, however, reported to be inactive.
U.S. Pat. No. 3,644,631 (to Pachter, et al.) discloses the generic formula: ##STR8## wherein, e.g., R.sub.1 can be H, lower alkyl, or phenyl; R.sub.2,R.sub.4, and R.sub.5 can be H, lower alkyl, or halo-; and Ar can be substituted aryl including tri-substituted by groups including lower alkyl or hydroxy. These compounds are proposed for anti-inflammatory uses. The disclosure, however, focuses on substitutions to the pyrrole; it does not encompass branched-chain-alkyl-substituted aryl groups, nor aryl groups with both alkyl and hydroxy substitutions.
It has been suggested that inhibition of the enzymes cyclooxygenase and lipoxygenase may be involved in the activity of anti-inflammatory agents. The involvement of antioxidant activity has also been suggested.